Synthesis, chemical reactivity and fungicidal activity of pyrido[1,2-b][1,2,4]triazine derivatives

Abstract

A síntese de alguns novos derivados de pirido [1,2-b][1,2,4]triazinas (2-12) foi obtida através da ciclocondensação de 4-aril-1,6-diamino-2-oxo-1,2-diidropiridina-3,5-dicarbonitrilas (1a,b) com compostos α,β-bifuncionais. Foram também preparadas pirido[1,2:2´,3´]triazino[5´,6´-f] triazinas (13)(14). O comportamento de 1a,b frente às interações com indol-2,3-diona e seu análogo N-acetil foi estudado em diferentes condições de reação. As estruturas dos novos produtos foram deduzidas a partir de análise elementar e de dados espectroscópicos (UV, IR, 1 H RMN, 13C RMN e espectrometria de massas). Os novos compostos sintetizados foram testados quanto à atividade antifungos.The synthesis of some new pyrido[1,2-b][1,2,4]triazines (2-12) was achieved by cyclocondensation of 4-aryl-1,6-diamino-2-oxo-1,2-dihydropyridine-3,5-dicarbonitriles (1a,b) with α,β-bifunctional compounds. Pyrido[1,2:2´,3´]triazino[5´,6´-f]triazines (13-14) were also prepared. The behavior of 1a,b toward interactions with indole-2,3-dione and its N-acetyl analogue have been studied under different reaction conditions. The structures of the new products have been deduced from elemental analysis and spectral data (UV, IR, 1 H NMR, 13 C NMR and mass spectra). The new synthesized compounds were screened for their antifungal activities.

1,2,4-Triazine Chemistry Part I: Orientation of cyclization reactions of functionalized 1,2,4-triazine derivatives

“…These effects at position 6 of 3-hydrazino-5-hydroxy-1,2,4-triazine (1) on the orientation of cyclization to form 1,2,4-triazolo [1,2,4]triazines, was examined by Daunis et al [13]. Thus, when R was an electron attracting group, 1,2,4-triazolo [3,4-c] [1,2,4]triazines (2) were formed in the presence of acidic (HCO2H or AcOH) or neutral [HC(OEt)3 or MeC(EtO)3] media. On the other hand, when R was an electron donating group and the reagent was acidic (HCO2H or AcOH), 1,2,4-triazolo [4,3-b] [1,2,4]triazine derivatives (3) were formed.…”

“…Thus, when R was an electron attracting group, 1,2,4-triazolo [3,4-c] [1,2,4]triazines (2) were formed in the presence of acidic (HCO2H or AcOH) or neutral [HC(OEt)3 or MeC(EtO)3] media. On the other hand, when R was an electron donating group and the reagent was acidic (HCO2H or AcOH), 1,2,4-triazolo [4,3-b] [1,2,4]triazine derivatives (3) were formed. Compound 4 was obtained as by-product with 2 and the amount of 4 increased with long reaction time (Scheme 1).…”

“…Also, hydrazinolysis of 39 using N-acetylhydrazine yielded the 1H-4,5-diphenyl-5H-6-methyl-1,2,4-triazolo [3,4-c] [1,2,4] triazine (40) and not (41) (Scheme 12) [25]. The reaction proceeded through nucleophilic displacement of ethylthio group, followed by cyclization at N-4 and not N-2 atom.…”

“…On the other hand, the reactivity of compound 42 towards both nucleophilic and electrophilic reagents in different medium have been reported [28] where the nucleophilicity increase in order S> O> N. Thus, treatment of 42 with phenacyl bromide in refluxing DMF yielded 1,2,4-triazino [3,4-b] [1,3,4]thiadiazin-4-one (47) while its boiling with glyoxylic acid in DMF followed by careful dehydration with concentrated H2SO4 afforded 1,2,4-triazino [3,4-…”

“…Furthermore, many heterocyclic systems bearing 1,2,4-triazines are found to exhibit remarkable pharmacological effects [1][2][3][4][5]. In search for new anti-HIV and anticancer agents, some additional heterocyclic moieties were incorporated in the 1,2,4-triazine nucleus via the interaction between functionalized 1,2,4-triazines with various nucleophilic and electrophilic reagents in different media [6][7][8][9][10][11][12].…”